Implications of reinfection for Hepatitis C elimination among HIV-infected and uninfected people who inject drugs

艾滋病毒感染者和未感染者注射吸毒者再​​次感染对消除丙型肝炎的影响

• 批准号: 10080970
• 负责人: Kyra H Grantz
• 金额: $ 5.37万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080970
• 关键词: Acute; Address; Affect; Aftercare; Antiviral Agents; Antiviral Therapy; Baltimore; Behavioral; Biological Factors; Communities; Data; Demographic Factors; Disease; Disease Progression; Effectiveness; Epidemiology; Event; Exposure to; Funding; Genetic; Genetic study; HIV; HIV Infections; Harm Reduction; Health; Hepatitis C; Hepatitis C Acquisition; Hepatitis C Prevalence; Hepatitis C Therapy; Hepatitis C Viremia; Hepatitis C virus; Incidence; Individual; Infection; Injecting drug user; Injections; Intervention; Lead; Measures; Methods; Modeling; Molecular; Morbidity - disease rate; National Institute of Drug Abuse; Pattern; Policies; Population; Prevention; Prevention strategy; Public Health; Public Health Practice; Relapse; Research; Risk; Risk Factors; Role; Seroprevalences; Study models; Subgroup; Substance Use Disorder; Target Populations; Testing; Time; Treatment Failure; United States; Ursidae Family; Viral; Viremia; Visit; base; career; chronic infection; co-infection; cohort; comorbidity; curative treatments; design; epidemiologic data; evidence base; experience; high risk; improved; individual variation; infection risk; markov model; mathematical model; mortality; next generation; next generation sequencing; novel; pathogen; programs; public health intervention; social; social factors; transmission process; treatment strategy

PROJECT SUMMARY / ABSTRACT Hepatitis C virus (HCV) infection and HCV-HIV coinfections are significant causes of morbidity and mortality among people who inject drugs (PWID). HCV prevalence among PWID can exceed 90% in high burden settings, and incidence remains high in the US following the changing epidemiology of substance use disorders. Highly effective, curative treatment for HCV is available, and calls have been made for the expansion of treatment-as- prevention and harm reduction programs to eliminate HCV globally. While modeling studies have indicated moderate to high treatment coverage may achieve elimination targets among PWID by 2030, such models often do not fully account for individual heterogeneity and longitudinal patterns in HCV risk. Even low rates of HCV reinfection can lead to pathogen persistence, a phenomenon that may be particularly important when considering micro-elimination among PWID living with HIV. However, traditional methods to measure HCV risk result in substantial misclassification when long testing intervals lead to frequent unobserved HCV exposure events (e.g., clearance-reinfection events occurring between study visits classified as a single chronic infection). Here, we will leverage rich epidemiologic and molecular data from a 30-year cohort of HIV-infected and uninfected PWID in Baltimore, MD USA (the ALIVE study) to explore the feasibility of HCV elimination in a high burden setting. We will use hidden Markov models which account for unobserved exposures to estimate HCV risk across individuals' injection careers. We will use next-generation genetic sequencing data to quantify risk of reinfection and treatment failure among individuals known to have received directly acting antiviral therapy and returned with post-treatment viremia. In both aims, we will consider the role of HIV coinfection as a modifier of HCV risk. Together, these aims will allow for identification of individuals and time periods within injection careers in which expected HCV reinfection risk is high. With this improved understanding of the individual and temporal variance in HCV reinfection risk, we will generate evidence-based assessments of various policies and strategies for delivering HCV treatment and harm reduction using dynamic transmission models, including targeted strategies among HIV-infected PWID. This project will provide critical guidance for policymakers and public health officials on the design and implementation of effective HCV elimination strategies among HIV-infected and uninfected PWID.

项目摘要/摘要 丙型肝炎病毒(丙型肝炎病毒)感染和丙型肝炎病毒-艾滋病毒混合感染是发病率和死亡率的重要原因 在注射毒品者中(PWID)。在高负担环境中，PWID中的丙型肝炎病毒感染率可超过90%， 随着物质使用障碍流行病学的变化，美国的发病率仍然很高。高度 丙型肝炎的有效、根治性治疗是可用的，并呼吁扩大治疗范围。 预防和减少危害计划，以在全球消除丙型肝炎病毒。虽然建模研究表明 中到高的治疗覆盖率可能在2030年前在PWID中实现消除目标，这种模式通常 不要完全考虑丙型肝炎病毒风险的个体异质性和纵向模式。即使丙型肝炎病毒感染率很低 再感染可能导致病原体持续存在，这一现象在考虑到 艾滋病毒携带者中的微量消除。然而，传统的测量丙型肝炎病毒风险的方法会导致 当长的测试间隔导致频繁的未观察到的丙型肝炎病毒暴露事件时的严重错误分类(例如， 清除-在两次研究访问之间发生的再感染事件，归类为单一慢性感染)。 在这里，我们将利用来自30年来感染艾滋病毒和艾滋病的队列的丰富流行病学和分子数据 美国马里兰州巴尔的摩未感染的PWID(The Alive研究)探索在较高水平消除丙型肝炎的可行性 负担设定。我们将使用隐马尔可夫模型来估计丙型肝炎病毒 个人注射职业生涯中的风险。我们将使用下一代基因测序数据来量化 已知接受过直接作用抗病毒治疗的患者中的再感染和治疗失败 带着治疗后的病毒血症回来。在这两个目标中，我们将考虑艾滋病毒合并感染作为一种修饰因素的作用 丙型肝炎病毒风险。总之，这些目标将允许识别注射职业生涯中的个人和时间段 其中预期的丙型肝炎病毒再感染风险很高。随着对个体和时间的理解的提高， 丙型肝炎病毒再感染风险的差异，我们将对各种政策和战略进行循证评估 使用动态传播模型提供丙型肝炎病毒治疗和减少危害，包括靶向传播模型 在感染艾滋病毒的PWID中采取的策略。该项目将为政策制定者和公众提供关键指导 卫生官员介绍在艾滋病毒感染者中设计和实施有效的丙型肝炎病毒消除策略 和未感染的PWID。